Chronic CD27-CD70 costimulation promotes type 1-specific polarization of effector Tregs

Front Immunol. 2023 Mar 13:14:1023064. doi: 10.3389/fimmu.2023.1023064. eCollection 2023.

Abstract

Introduction: Most T lymphocytes, including regulatory T cells, express the CD27 costimulatory receptor in steady state conditions. There is evidence that CD27 engagement on conventional T lymphocytes favors the development of Th1 and cytotoxic responses in mice and humans, but the impact on the regulatory lineage is unknown.

Methods: In this report, we examined the effect of constitutive CD27 engagement on both regulatory and conventional CD4+ T cells in vivo, in the absence of intentional antigenic stimulation.

Results: Our data show that both T cell subsets polarize into type 1 Tconvs or Tregs, characterized by cell activation, cytokine production, response to IFN-γ and CXCR3-dependent migration to inflammatory sites. Transfer experiments suggest that CD27 engagement triggers Treg activation in a cell autonomous fashion.

Conclusion: We conclude that CD27 may regulate the development of Th1 immunity in peripheral tissues as well as the subsequent switch of the effector response into long-term memory.

Keywords: CD27 costimulation; CXCR3; dendritic cells; eomes; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / metabolism
  • CD27 Ligand / metabolism
  • Humans
  • Mice
  • T-Lymphocyte Subsets* / metabolism
  • T-Lymphocytes, Regulatory* / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7* / metabolism

Substances

  • Antigens
  • CD27 Ligand
  • CD70 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Grants and funding

The work was supported was the National Fund for Scientific Research (FNRS), the European Regional Development Fund (ERDFWallonia BioMed 2014-2020-LIV 45-20), Wallonia (Programme d’Excellence Food4GUT) and grants from the Fonds Jean Brachet and the Fonds Hoguet.